G. Program Summary/Abstract: Project 3 The overarching goal of this project is to test the hypothesis that isothiocyanates (ITCs) produced in the leaves of moringa (Moringa oleifera Lam) provide an effective, chemically stable and practical alternative to instable and volatile ITCs produced by plants of the crucifer family (Brassicaceae) for building resiliency and maintaining normal metabolism. Plant-produced ITCs associated with ?superfoods? in the crucifer family are among some of the most biologically active compounds isolated from plants. However, ITCs formed in crucifers, such as broccoli, share inherent thermolability and chemical instability that greatly complicate their use in human medicine. Interestingly, moringa ITCs (MICs) contain an additional sugar residue, conferring much greater stability and appear as solids at room termperature. Stable ITCs are extremely rare in nature and virtually unexplored as alternatives to beneficial crucifer ITCs. We have developed a simple, single-step extraction/biotransformation method which effectively converts moringa glucosinolates into MICs resulting in a moringa concentrate (MC) containing 3% MICs. Our preliminary data have shown that MC and its isolated MICs have potential anti- inflammatory, anti-diabetic and anti-obesity effects. Early stages of the proposed project will concentrate on moringa extract optimization, characterization and establishment of quality standards and botanical authentication criteria (Aim 1). Subsequent research will focus on the molecular and physiological mechanisms involved in its bioavailability and action using global approaches based on metabolic crosstalk, gut microbiome and transcriptomics (Aim 2 & 3). Through close integration with the Botanical and Integrative Biology Cores and in full collaboration with other projects we have designed these aims to test whether the enhanced stability, combined with high bioavailability and bioactivity, makes moringa ITCs and MC promising botanical agents for maintaining and promoting resilience based on healthy metabolism and gut microbiome.